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PLoS Genetics

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https://www.readbyqxmd.com/read/28636662/differential-regulation-of-polarized-synaptic-vesicle-trafficking-and-synapse-stability-in-neural-circuit-rewiring-in-caenorhabditis-elegans
#1
Naina Kurup, Dong Yan, Karina Kono, Yishi Jin
Neural circuits are dynamic, with activity-dependent changes in synapse density and connectivity peaking during different phases of animal development. In C. elegans, young larvae form mature motor circuits through a dramatic switch in GABAergic neuron connectivity, by concomitant elimination of existing synapses and formation of new synapses that are maintained throughout adulthood. We have previously shown that an increase in microtubule dynamics during motor circuit rewiring facilitates new synapse formation...
June 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28636652/integrative-analysis-of-genomic-alterations-in-triple-negative-breast-cancer-in-association-with-homologous-recombination-deficiency
#2
Masahito Kawazu, Shinya Kojima, Toshihide Ueno, Yasushi Totoki, Hiromi Nakamura, Akiko Kunita, Wei Qu, Jun Yoshimura, Manabu Soda, Takahiko Yasuda, Natsuko Hama, Mihoko Saito-Adachi, Kazuhito Sato, Shinji Kohsaka, Eirin Sai, Masako Ikemura, Shigeru Yamamoto, Tomoko Ogawa, Masashi Fukayama, Keiichiro Tada, Yasuyuki Seto, Shinichi Morishita, Shoichi Hazama, Tatsuhiro Shibata, Yoshihiro Yamashita, Hiroyuki Mano
Triple-negative breast cancer (TNBC) cells do not express estrogen receptors, progesterone receptors, or human epidermal growth factor receptor 2. Currently, apart from poly ADP-ribose polymerase inhibitors, there are few effective therapeutic options for this type of cancer. Here, we present comprehensive characterization of the genetic alterations in TNBC performed by high coverage whole genome sequencing together with transcriptome and whole exome sequencing. Silencing of the BRCA1 gene impaired the homologous recombination pathway in a subset of TNBCs, which exhibited similar phenotypes to tumors with BRCA1 mutations; they harbored many structural variations (SVs) with relative enrichment for tandem duplication...
June 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28628665/a-chromosome-5q31-1-locus-associates-with-tuberculin-skin-test-reactivity-in-hiv-positive-individuals-from-tuberculosis-hyper-endemic-regions-in-east-africa
#3
Rafal S Sobota, Catherine M Stein, Nuri Kodaman, Isaac Maro, Wendy Wieland-Alter, Robert P Igo, Albert Magohe, LaShaunda L Malone, Keith Chervenak, Noemi B Hall, Mecky Matee, Harriet Mayanja-Kizza, Moses Joloba, Jason H Moore, William K Scott, Timothy Lahey, W Henry Boom, C Fordham von Reyn, Scott M Williams, Giorgio Sirugo
One in three people has been infected with Mycobacterium tuberculosis (MTB), and the risk for MTB infection in HIV-infected individuals is even higher. We hypothesized that HIV-positive individuals living in tuberculosis-endemic regions who do not get infected by Mycobacterium tuberculosis are genetically resistant. Using an "experiment of nature" design that proved successful in our previous work, we performed a genome-wide association study of tuberculin skin test positivity using 469 HIV-positive patients from prospective study cohorts of tuberculosis from Tanzania and Uganda to identify genetic loci associated with MTB infection in the context of HIV-infection...
June 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28628615/flipping-chromosomes-in-deep-sea-archaea
#4
Matteo Cossu, Catherine Badel, Ryan Catchpole, Danièle Gadelle, Evelyne Marguet, Valérie Barbe, Patrick Forterre, Jacques Oberto
One of the major mechanisms driving the evolution of all organisms is genomic rearrangement. In hyperthermophilic Archaea of the order Thermococcales, large chromosomal inversions occur so frequently that even closely related genomes are difficult to align. Clearly not resulting from the native homologous recombination machinery, the causative agent of these inversions has remained elusive. We present a model in which genomic inversions are catalyzed by the integrase enzyme encoded by a family of mobile genetic elements...
June 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28628612/novel-interplay-between-jnk-and-egfr-signaling-in-drosophila-dorsal-closure
#5
Tatyana Kushnir, Sharon Mezuman, Shaked Bar-Cohen, Rotem Lange, Ze'ev Paroush, Aharon Helman
Dorsal closure (DC) is a developmental process in which two contralateral epithelial sheets migrate to seal a large hole in the dorsal ectoderm of the Drosophila embryo. Two signaling pathways act sequentially to orchestrate this dynamic morphogenetic process. First, c-Jun N-terminal kinase (JNK) signaling activity in the dorsal-most leading edge (LE) cells of the epidermis induces expression of decapentaplegic (dpp). Second, Dpp, a secreted TGF-β homolog, triggers cell shape changes in the adjacent, ventrally located lateral epidermis, that guide the morphogenetic movements and cell migration mandatory for DC...
June 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28628608/tcp4-dependent-induction-of-constans-transcription-requires-gigantea-in-photoperiodic-flowering-in-arabidopsis
#6
Akane Kubota, Shogo Ito, Jae Sung Shim, Richard S Johnson, Yong Hun Song, Ghislain Breton, Greg S Goralogia, Michael S Kwon, Dianne Laboy Cintrón, Tomotsugu Koyama, Masaru Ohme-Takagi, Jose L Pruneda-Paz, Steve A Kay, Michael J MacCoss, Takato Imaizumi
Photoperiod is one of the most reliable environmental cues for plants to regulate flowering timing. In Arabidopsis thaliana, CONSTANS (CO) transcription factor plays a central role in regulating photoperiodic flowering. In contrast to posttranslational regulation of CO protein, still little was known about CO transcriptional regulation. Here we show that the CINCINNATA (CIN) clade of class II TEOSINTE BRANCHED 1/ CYCLOIDEA/ PROLIFERATING CELL NUCLEAR ANTIGEN FACTOR (TCP) proteins act as CO activators. Our yeast one-hybrid analysis revealed that class II CIN-TCPs, including TCP4, bind to the CO promoter...
June 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28628606/splicing-stimulates-sirna-formation-at-drosophila-dna-double-strand-breaks
#7
Karin Merk, Marco Breinig, Romy Böttcher, Stefan Krebs, Helmut Blum, Michael Boutros, Klaus Förstemann
DNA double-strand breaks trigger the production of locus-derived siRNAs in fruit flies, human cells and plants. At least in flies, their biogenesis depends on active transcription running towards the break. Since siRNAs derive from a double-stranded RNA precursor, a major question is how broken DNA ends can generate matching sense and antisense transcripts. We performed a genome-wide RNAi-screen in cultured Drosophila cells, which revealed that in addition to DNA repair factors, many spliceosome components are required for efficient siRNA generation...
June 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28617813/identification-of-padi2-as-a-novel-angiogenesis-regulating-gene-by-genome-association-studies-in-mice
#8
Mehrdad Khajavi, Yi Zhou, Amy E Birsner, Lauren Bazinet, Amanda Rosa Di Sant, Alex J Schiffer, Michael S Rogers, Subrahmanian Tarakkad Krishnaji, Bella Hu, Vy Nguyen, Leonard Zon, Robert J D'Amato
Recent findings indicate that growth factor-driven angiogenesis is markedly influenced by genetic variation. This variation in angiogenic responsiveness may alter the susceptibility to a number of angiogenesis-dependent diseases. Here, we utilized the genetic diversity available in common inbred mouse strains to identify the loci and candidate genes responsible for differences in angiogenic response. The corneal micropocket neovascularization assay was performed on 42 different inbred mouse strains using basic fibroblast growth factor (bFGF) pellets...
June 15, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28617799/p53-and-tap63-participate-in-the-recombination-dependent-pachytene-arrest-in-mouse-spermatocytes
#9
Marina Marcet-Ortega, Sarai Pacheco, Ana Martínez-Marchal, Helena Castillo, Elsa Flores, Maria Jasin, Scott Keeney, Ignasi Roig
To protect germ cells from genomic instability, surveillance mechanisms ensure meiosis occurs properly. In mammals, spermatocytes that display recombination defects experience a so-called recombination-dependent arrest at the pachytene stage, which relies on the MRE11 complex-ATM-CHK2 pathway responding to unrepaired DNA double-strand breaks (DSBs). Here, we asked if p53 family members-targets of ATM and CHK2-participate in this arrest. We bred double-mutant mice combining a mutation of a member of the p53 family (p53, TAp63, or p73) with a Trip13 mutation...
June 15, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28614350/ranking-and-characterization-of-established-bmi-and-lipid-associated-loci-as-candidates-for-gene-environment-interactions
#10
Dmitry Shungin, Wei Q Deng, Tibor V Varga, Jian'an Luan, Evelin Mihailov, Andres Metspalu, Andrew P Morris, Nita G Forouhi, Cecilia Lindgren, Patrik K E Magnusson, Nancy L Pedersen, Göran Hallmans, Audrey Y Chu, Anne E Justice, Mariaelisa Graff, Thomas W Winkler, Lynda M Rose, Claudia Langenberg, L Adrienne Cupples, Paul M Ridker, Nicholas J Wareham, Ken K Ong, Ruth J F Loos, Daniel I Chasman, Erik Ingelsson, Tuomas O Kilpeläinen, Robert A Scott, Reedik Mägi, Guillaume Paré, Paul W Franks
Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (G×E) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (Pv), G×E interaction effects (with smoking and physical activity), and marginal genetic effects (Pm). Correlations between Pv and Pm were stronger for SNPs with established marginal effects (Spearman's ρ = 0...
June 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28609436/cleavage-of-the-sun-domain-protein-mps3-at-its-n-terminus-regulates-centrosome-disjunction-in-budding-yeast-meiosis
#11
Ping Li, Hui Jin, Bailey A Koch, Rebecca L Abblett, Xuemei Han, John R Yates, Hong-Guo Yu
Centrosomes organize microtubules and are essential for spindle formation and chromosome segregation during cell division. Duplicated centrosomes are physically linked, but how this linkage is dissolved remains unclear. Yeast centrosomes are tethered by a nuclear-envelope-attached structure called the half-bridge, whose components have mammalian homologues. We report here that cleavage of the half-bridge protein Mps3 promotes accurate centrosome disjunction in budding yeast. Mps3 is a single-pass SUN-domain protein anchored at the inner nuclear membrane and concentrated at the nuclear side of the half-bridge...
June 13, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28604780/the-yeast-protein-kinase-sch9-adjusts-v-atpase-assembly-disassembly-to-control-ph-homeostasis-and-longevity-in-response-to-glucose-availability
#12
Tobias Wilms, Erwin Swinnen, Elja Eskes, Laura Dolz-Edo, Alice Uwineza, Ruben Van Essche, Joëlle Rosseels, Piotr Zabrocki, Elisabetta Cameroni, Vanessa Franssens, Claudio De Virgilio, Gertien J Smits, Joris Winderickx
The conserved protein kinase Sch9 is a central player in the nutrient-induced signaling network in yeast, although only few of its direct substrates are known. We now provide evidence that Sch9 controls the vacuolar proton pump (V-ATPase) to maintain cellular pH homeostasis and ageing. A synthetic sick phenotype arises when deletion of SCH9 is combined with a dysfunctional V-ATPase, and the lack of Sch9 has a significant impact on cytosolic pH (pHc) homeostasis. Sch9 physically interacts with, and influences glucose-dependent assembly/disassembly of the V-ATPase, thereby integrating input from TORC1...
June 12, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28604778/p63-exerts-spatio-temporal-control-of-palatal-epithelial-cell-fate-to-prevent-cleft-palate
#13
Rose Richardson, Karen Mitchell, Nigel L Hammond, Maria Rosaria Mollo, Evelyn N Kouwenhoven, Niki D Wyatt, Ian J Donaldson, Leo Zeef, Tim Burgis, Rognvald Blance, Simon J van Heeringen, Hendrik G Stunnenberg, Huiqing Zhou, Caterina Missero, Rose Anne Romano, Satrajit Sinha, Michael J Dixon, Jill Dixon
Cleft palate is a common congenital disorder that affects up to 1 in 2500 live births and results in considerable morbidity to affected individuals and their families. The aetiology of cleft palate is complex with both genetic and environmental factors implicated. Mutations in the transcription factor p63 are one of the major individual causes of cleft palate; however, the gene regulatory networks in which p63 functions remain only partially characterized. Our findings demonstrate that p63 functions as an essential regulatory molecule in the spatio-temporal control of palatal epithelial cell fate to ensure appropriate fusion of the palatal shelves...
June 12, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28604776/the-arabidopsis-leucine-rich-repeat-receptor-kinase-mik2-lrr-kiss-connects-cell-wall-integrity-sensing-root-growth-and-response-to-abiotic-and-biotic-stresses
#14
Dieuwertje Van der Does, Freddy Boutrot, Timo Engelsdorf, Jack Rhodes, Joseph F McKenna, Samantha Vernhettes, Iko Koevoets, Nico Tintor, Manikandan Veerabagu, Eva Miedes, Cécile Segonzac, Milena Roux, Alice S Breda, Christian S Hardtke, Antonio Molina, Martijn Rep, Christa Testerink, Grégory Mouille, Herman Höfte, Thorsten Hamann, Cyril Zipfel
Plants actively perceive and respond to perturbations in their cell walls which arise during growth, biotic and abiotic stresses. However, few components involved in plant cell wall integrity sensing have been described to date. Using a reverse-genetic approach, we identified the Arabidopsis thaliana leucine-rich repeat receptor kinase MIK2 as an important regulator of cell wall damage responses triggered upon cellulose biosynthesis inhibition. Indeed, loss-of-function mik2 alleles are strongly affected in immune marker gene expression, jasmonic acid production and lignin deposition...
June 12, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28604770/pervasive-antagonistic-interactions-among-hybrid-incompatibility-loci
#15
Rafael F Guerrero, Christopher D Muir, Sarah Josway, Leonie C Moyle
Species barriers, expressed as hybrid inviability and sterility, are often due to epistatic interactions between divergent loci from two lineages. Theoretical models indicate that the strength, direction, and complexity of these genetic interactions can strongly affect the expression of interspecific reproductive isolation and the rates at which new species evolve. Nonetheless, empirical analyses have not quantified the frequency with which loci are involved in interactions affecting hybrid fitness, and whether these loci predominantly interact synergistically or antagonistically, or preferentially involve loci that have strong individual effects on hybrid fitness...
June 12, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28604769/lokiarchaea-are-close-relatives-of-euryarchaeota-not-bridging-the-gap-between-prokaryotes-and-eukaryotes
#16
Violette Da Cunha, Morgan Gaia, Daniele Gadelle, Arshan Nasir, Patrick Forterre
The eocyte hypothesis, in which Eukarya emerged from within Archaea, has been boosted by the description of a new candidate archaeal phylum, "Lokiarchaeota", from metagenomic data. Eukarya branch within Lokiarchaeota in a tree reconstructed from the concatenation of 36 universal proteins. However, individual phylogenies revealed that lokiarchaeal proteins sequences have different evolutionary histories. The individual markers phylogenies revealed at least two subsets of proteins, either supporting the Woese or the Eocyte tree of life...
June 12, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28598966/joint-modeling-of-genetically-correlated-diseases-and-functional-annotations-increases-accuracy-of-polygenic-risk-prediction
#17
Yiming Hu, Qiongshi Lu, Wei Liu, Yuhua Zhang, Mo Li, Hongyu Zhao
Accurate prediction of disease risk based on genetic factors is an important goal in human genetics research and precision medicine. Advanced prediction models will lead to more effective disease prevention and treatment strategies. Despite the identification of thousands of disease-associated genetic variants through genome-wide association studies (GWAS) in the past decade, accuracy of genetic risk prediction remains moderate for most diseases, which is largely due to the challenges in both identifying all the functionally relevant variants and accurately estimating their effect sizes...
June 9, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28594826/a-highly-specific-phage-defense-system-is-a-conserved-feature-of-the-vibrio-cholerae-mobilome
#18
Brendan J O'Hara, Zachary K Barth, Amelia C McKitterick, Kimberley D Seed
Vibrio cholerae-specific bacteriophages are common features of the microbial community during cholera infection in humans. Phages impose strong selective pressure that favors the expansion of phage-resistant strains over their vulnerable counterparts. The mechanisms allowing virulent V. cholerae strains to defend against the ubiquitous threat of predatory phages have not been established. Here, we show that V. cholerae PLEs (phage-inducible chromosomal island-like elements) are widespread genomic islands dedicated to phage defense...
June 8, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28594821/dynamics-of-dna-methylomes-underlie-oyster-development
#19
Guillaume Riviere, Yan He, Samuele Tecchio, Elizabeth Crowell, Michaël Gras, Pascal Sourdaine, Ximing Guo, Pascal Favrel
DNA methylation is a critical epigenetic regulator of development in mammals and social insects, but its significance in development outside these groups is not understood. Here we investigated the genome-wide dynamics of DNA methylation in a mollusc model, the oyster Crassostrea gigas, from the egg to the completion of organogenesis. Large-scale methylation maps reveal that the oyster genome displays a succession of methylated and non methylated regions, which persist throughout development. Differentially methylated regions (DMRs) are strongly regulated during cleavage and metamorphosis...
June 8, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28552952/asymmetric-regulation-of-quorum-sensing-receptors-drives-autoinducer-specific-gene-expression-programs-in-vibrio-cholerae
#20
Amanda Hurley, Bonnie L Bassler
Quorum sensing (QS) is a mechanism of chemical communication that bacteria use to monitor cell-population density and coordinate group behaviors. QS relies on the production, detection, and group-wide response to extracellular signal molecules called autoinducers. Vibrio cholerae employs parallel QS circuits that converge into a shared signaling pathway. At high cell density, the CqsS and LuxPQ QS receptors detect the intra-genus and inter-species autoinducers CAI-1 and AI-2, respectively, to repress virulence factor production and biofilm formation...
May 26, 2017: PLoS Genetics
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